Magister Scientiae (Medical Bioscience) - MSc(MBS) / The aim of this study was to determine and evaluate the prevalence of TB infection, active TB cases and the risk factors associated with TB infection in Macassar Camp in Macassar (about 40 km from Cape Town on the False Bay coast, with a population of 369). The study design of this epidemiological study was a cross sectional study with a descriptive and an analytic component A comparison between the Mantoux, TB ELISA and X-ray screening tests was performed first. A description of the origin, discovery, characteristics and pathology associated with Mycobacterium tuberculosis as well as the development of the TB epidemic on a global, national and local level, is given. TB was first described to give a South African perspective of the TB epidemic and both the "Virgin Soil" and "Non-Virgin Soil" theory of TB was reviewed. Secondly, ~he TB infection rate in Macassar Camp and the risk factors as well as the determinants of TB infection with regards to overcrowding, ventilation, primary food subsistence level rating (PFSL), social class and employment status were evaluated The third aspect of the study compares prevalence/incidence rates of TB to clinical diagnosis with regards to the symptomatology, radiographs, sputum microscopy, bacteriology and Mantoux test. Lastly the Mantoux test was compared with the TB ELISA test with regards to diagnosis of infection, in new and past confirmed TB cases. The first part of the survey involved the measurement of openable window area and the floor area of each Camp dwelling (to determine if ventilation was within required limits), during the administration of a household questionnaire which was designed to determine the number of occupants, rooms, income, food expenditure per household in the Camp. A personal questionnaire was administered to all Macassar Camp residents to elicit information on demography, knowledge and attitudes to TB, history of past TB, TB contacts, alcohol intake and smoking habits, occupation and BCG status. The Mantoux test were performed on consenting Camp residents in addition to the collection of 5 ml of blood for the TB ELISA tests. The Camp residents heights and weights were recorded prior to the miniature mass chest radiographs being taken. The 'TB suspects' sputa were collected for the microscopy and bacteriological examination. A review of the clinical records of TB patients in the Macassar/Stellenbosch area was also undertaken. The response rate to the household questionnaire was 60 from 63 (95,2%) dwelling units. Whereas the response rate to the personal questionnaire was 296 (80,2%). As for the Mantoux and TB ELISA tests the response rate was 209 (56,6%). Of the 60 dwelling units, 43 (71,7%) were calculated (according to . Batsons Index) to be crowded and 16 (26,7%) dwelling units had an overall ventilation of less than 5% (below the required regulation). There were significantly (p<0,005) more male than female smokers and only 78 (34,2%) of the residents regarded themselves as non-smokers. A similar trend was noted with regards to the alcohol intake of the residents, where only 86 (37,7%) regarded themselves as teetotallers, with significantly more (p=0,003) male than female alcohol consumers. Females sc6red significantly (p=0,002) better than the males with regards to TB knowledge and awareness. Only 199 (67,2%), residents indicated that they had had BeG vaccination. Of the 296 residents responding to the survey, there were 83 children aged 14 years or less. And only 74 of these children were confirmed to have been vaccinated with BeG, resulting in a 89,2% BeG coverage. Two (4,7%) of the 43 children aged 14 years or less were determined to be malnourished on the basis of Z-scores (below -2SD) taking into account height for age as well as weight for height.

Mycobacterium tuberculosis (Mtb) is the pathogen that causes Tuberculosis (TB) and is responsible for an average of 1.5 million deaths annually. Although a treatment regimen does exist, Multi-Drug Resistant (MDR-TB) and eXtremely Drug Resistant (XDR-TB) TB strains are becoming a more prevalent concern partly due to failure of patient compliance with the current six to nine month drug treatment regimen. The current diagnostic methods are not able to identify these MDR and XDR-TB strains efficiently therefore more effective point-of-care (POC) diagnostics and drug susceptibility testing (DST) are urgently needed to detect drug resistance and facilitate prompt, appropriate treatment plans. In order to detect TB and efficiently identify drug resistance, this project seeks to develop a novel diagnostic technology based on deoxyribozyme (DNAzyme) sensors. The overall goal of this project is to create an assay which combines Polymerase Chain Reaction (PCR) and DNAzymes to identify drug resistance conferring Single Nucleotide Polymorphisms (SNPs). To safely test the ability of DNAzyme sensors to detect SNPs indicative of multi-drug resistant TB, we have constructed a panel of drug resistant (drugR) nonpathogenic M. bovis BCG. We have designed a multiplex PCR that amplifies 6 chromosomal regions of the genome necessary for the species specific detection of TB and determination of a drug susceptibility profile based on the presence of SNPs. To improve the sensitivity and selectivity of the detection and DST of Mtb, we have designed and optimized DNAzyme sensor assays combined with multiplex PCR analytes that will enable the rapid, POC detection of drug resistance. This work aims to develop novel tools for the prompt and specific diagnosis of TB allowing for the implementation of an iv effective treatment regimen that will ultimately lessen transmission and control the emerging global threat of MDR and XDR-TB.

Tuberculosis (TB) is a respiratory disease caused by Mycobacterium tuberculosis (Mtb) that kills around 1.3 million people annually. Multi-drug resistant TB (MDR-TB) strains are increasingly encountered, in part resulting from shortcomings of current TB drug regimens that last between six to nine months. Patients may stop taking the antibiotics during their allotted regimen, leading to drug resistant TB strains. Novel drug screening platforms are therefore necessary to find drugs effective against MDR-TB. In order to discover compounds that target under-exploited pathways that may be essential only in vivo, the proposed screening platform will use a novel approach to drug discovery by blocking essential protein-protein interactions (PPI). In Mtb, PPI can be monitored by mycobacterial protein fragment complementation (M-PFC). This project will re-engineer the M-PFC assay to include the red fluorescent mCherry reporter for increased efficiency and sensitivity in high-throughput screening applications. To optimize the mCherry assay, we have developed fluorescent M-PFC reporter strains to monitor distinct PPI required for Mtb virulence: homodimerization of the dormancy regulator DosR. A drug screen will then identify novel compounds that inhibit this essential PPI. The screen will involve positional-scanning combinatorial synthetic libraries, which are made up of chemical compounds with varying side chains. This work will develop novel tools for TB drug discovery that could identify new treatments for the emerging world threat of MDR-TB.

This dissertation is a challenge to the Pentecostal churches, particularly, the Apostolic Faith Mission Church in Tumahole, to take an action in meeting the challenges posed by HIV/AIDS. This disease, HIV/AIDS, is the latest enemy to human life that the nations are faced with. In the newspapers like Sowetan, there is an article almost daily about HIV and AIDS. In this dissertation, I have tried to show shocking figures of how this disease is spreading in Africa. The seriousness of the disease, unlike other diseases, is its in curability. The secular organisations are far ahead of the churches in as far as the relevant programmes on combating HIV/AIDS are concerned. Despite these massive programmes, the disease is spreading like the wild fire. Deducing from this background, it is no longer the question of whether the Pentecostal churches have any role to play, but what specific role should the church play in this challenge. In this challenging times, many people look at the church as one of the most important institute that would play a positive role in bringing hope to the hopeless. / Christian Spirituality, Church History and Missiology / M. Th. (Missiology (Urban Ministry))

This dissertation is a challenge to the Pentecostal churches, particularly, the Apostolic Faith Mission Church in Tumahole, to take an action in meeting the challenges posed by HIV/AIDS. This disease, HIV/AIDS, is the latest enemy to human life that the nations are faced with. In the newspapers like Sowetan, there is an article almost daily about HIV and AIDS. In this dissertation, I have tried to show shocking figures of how this disease is spreading in Africa. The seriousness of the disease, unlike other diseases, is its in curability. The secular organisations are far ahead of the churches in as far as the relevant programmes on combating HIV/AIDS are concerned. Despite these massive programmes, the disease is spreading like the wild fire. Deducing from this background, it is no longer the question of whether the Pentecostal churches have any role to play, but what specific role should the church play in this challenge. In this challenging times, many people look at the church as one of the most important institute that would play a positive role in bringing hope to the hopeless. / Christian Spirituality, Church History and Missiology / M. Th. (Missiology (Urban Ministry))